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Lipidomic analysis of carrageenan‐induced hyperalgesia reveals bilateral eicosanoid production in the spinal cord
Author(s) -
Dumlao Darren Sabio,
Buczynski Mathew,
Svensson Camilla,
Fitzsimmons Bethany,
Wirkus Jennifer,
Jacobsen Faith,
Hua XiaoYing,
Yaksh Tony,
Dennis Edward
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.475.2
Subject(s) - hyperalgesia , anandamide , chemistry , eicosanoid , endocannabinoid system , lipidomics , pharmacology , ketorolac , lipoxygenase , carrageenan , lipid signaling , cyclooxygenase , spinal cord , morphine , lipid metabolism , nociception , arachidonic acid , analgesic , biochemistry , enzyme , medicine , cannabinoid receptor , receptor , psychiatry , agonist
Using a high throughput mass spectrometric lipidomics approach, we determined the contribution of bioactive lipids to carrageenan‐induced hyperalgesia. Quantitative analysis of CSF and spinal cord tissue for 171 different eicosanoids, ethanolamides and fatty acids revealed 102 distinct lipid species. There was a bilateral time‐dependent increase of 12‐lipoxygenase (12‐LOX) metabolites at 2 hours, cyclooxygenase (COX) metabolites at 8 hours, and anandamide between 12 and 24 hours in spinal cord. Systemic treatment with morphine, the COX inhibitor ketorolac, or the LOX inhibitor NDGA were used to investigate the correlation between spinal bioactive lipid levels and hyperalgesia. The inhibitors reduced allodynia but affected lipid profiles differentially. Morphine did not alter the lipid profile, while ketorolac and NDGA caused a global reduction of many bioactive lipid mediators. These findings suggest that COX and 12‐LOX play an important role in the induction of carrageenan mediated hyperalgesia potentially via cross talk between their pathways. This work was supported by GM64611 and GM069338 (E.A.D.).